Insulin like growth factor-1 (IGF-1) is a protein that promotes the growth and survival of cardiomyocytes. Mice deficient in IGF-1 exhibit increased apoptosis following myocardial infarction (Palmen, et al., Cardiovasc. Res. 50:516-524 (2001)), whereas cardiac-specific IGF-1 overexpression protects against myocyte apoptosis and ventricular dilation following infarction (Li, et aL, J. Clin. Invest. 100:1991-1999 (1997); Torella, et al., Circ. Res. 94:514-524 (2004)). IGF-1 overexpression also increases cardiac stem cell number and growth, leading to an increase in myocyte turnover and function in the aging heart. Following infarction, IGF-1 promotes engraftment, differentiation, and functional improvement of embryonic stem cells transplanted into myocardium (Kofidis, et aL, Stem Cells 22:1239-1245 (2004)). In addition, serum levels of IGF-1 correlate inversely with the risk of congenital heart failure in a subset of elderly patients (Vasan, et al., Ann. Intern. Med. 139:642-648 (2003)).
The characteristics described above make IGF-1 an attractive therapeutic agent for patients that have experienced damage to cardiac tissue, e.g., patients that have undergone a myocardial infarction. However, IGF-1 is a small protein that diffuses readily through tissues. As a result, it is difficult to keep a high concentration of this factor at a site of tissue damage for a prolonged period of time. One approach that has been taken to maintain a high local concentration is to attach IGF-1 to a self-assembling biological membrane (see US20060088510). Using a rat model of myocardial infarction, it was found that when this membrane is implanted along with neonatal cardiomyocytes, the survival and growth of the implanted cells is improved relative to cells implanted with unbound IGF-1. Thus, the ability of the cells to colonize the damaged heart and improve function is increased. Using a similar approach, positive results were also obtained using PDGF (US20060148703). Although these results are promising, alternative procedures that avoid the necessity of constructing and implanting membranes would be desirable.